The object of this project is to measure levels of neutral proteases, ribonucleases, and esterases as a function of muscle innervation in an attempt to elucidate the role of the nerve in control of the degradative phase of muscle protein and nucleic acid turnover. The enzyme systems to be studied are (a) N-acetyl-L-phenylalanine ethyl esterase, (b) an insoluble phenylalanine releasing enzyme system, (c) a Ca ions-dependent protease, (d) RNase I, and (e) "alkaline" RNase II and its inhibitor. The following will be undertaken: (1) Further characterization of the enzymic properties of the phenylalanine releasing system. (2) More detailed study of the time course of activity changes for the five neutral hydrolases listed as a function of skeletal muscle denervation and reinnervation including the influence of site of nerve section or damage and the influence of the presence or absence of factors such as active or passive tension. (3) Study of the effect of nerve constriction and release of constriction as compared to the results of study 2. (4) Study of the effects of cross-innervation as related to study 2. (5) Comparison of the activity pattern changes described to those found in other animal and human neuromuscular abnormalities to help resolve questions of neurogenic versus myogenic influences. (6) Comparative studies on the effects of denervation of diseased muscle on neutral hydrolase patterns with the aim that the response may help elucidate disease-related defects in the mechanisms controlling protein turnover. (7) Comparison of nerve-related activity pattern changes to those characteristic of embryonic, fetal, and postnatal development and to hormonal and use-related influences. (8) Further development and application of histochemical approaches to correlate with the biochemical studies described. (9) Pilot studies of effector influences on hydrolase systems in muscle and nerve-muscle tissue cultures.